The general biosynthetic pathway for ubiquinone is rather well established in prokaryotic systems but in eukaryotes there are several aspects which are still uncertain. These deal with 1) the stage of polyprenylation of the 3-position of the precursor of the quinone nucleus widely recognized to be 4-hydroxybenzoate. 2) The decarboxylation step: whether it immediately follows prenylation or occurs after the 5-position has been hydroxylated and O-methylated. 3) Which metabolic pathway of tyrosine gives rise to the potential aromatic precursor. These questions are raised because we have recently observed (Nambudiri et al., Fed. Proc. (1976) 35, 1644) that in addition to 4-hydroxybenzoate, vanillic acid (3-methoxy-4-hydroxybenzoate) and protocatechuic acid (3,4-dihydroxybenzoic acid) can also be prenylated by the 4-hydroxybenzoate: polyprenyl transferase in rat liver, heart, and brain preparations. Protocatechuic acid can also be incorporated into ubiquinone in liver. Of further significance is the fact that we have observed that these compounds can also be generated from the catabolism of norepinephrine, thus providing a direct link between catecholamine metabolism and ubiquinone synthesis. These relationships may have clinical significance and are being further investigated in our laboratory.